Molecular links between mitochondrial dysfunctions and schizophrenia

Abstract

Schizophrenia is a complex neuropsychiatric disorder with both neurochemical and neurodevelopmental components in the pathogenesis. Growing pieces of evidence indicate that schizophrenia has pathological components that can be attributable to the abnormalities of mitochondrial function, which is supported by the recent finding suggesting mitochondrial roles for Disrupted-in-Schizophrenia 1 (DISC1). In this minireview, we briefly summarize the current understanding of the molecular links between mitochondrial dysfunctions and the pathogenesis of schizophrenia, covering recent findings from human genetics, functional genomics, proteomics, and molecular and cell biological approaches.

Fig. 1.

DISC1-Mitofilin complex regulates mitochondrial functions. DISC1 is localized into intermembrane space of mitochondria and forms a functional complex with Mitofilin. Functional deficiency of DISC1 leads to loss of stability of Mitofilin, resulting in a number of mitochondrial dysfunctions, such as, decrease of NADH dehydrogenase activity, reduction of ATP contents, aberrant function of MAO, and perturbed calcium dynamics.